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https://www.readbyqxmd.com/read/27916980/the-immunopathogenesis-of-seropositive-rheumatoid-arthritis-from-triggering-to-targeting
#1
Vivianne Malmström, Anca I Catrina, Lars Klareskog
Patients with rheumatoid arthritis can be divided into two major subsets characterized by the presence versus absence of antibodies to citrullinated protein antigens (ACPAs) and of rheumatoid factor (RF). The antibody-positive subset of disease, also known as seropositive rheumatoid arthritis, constitutes approximately two-thirds of all cases of rheumatoid arthritis and generally has a more severe disease course. ACPAs and RF are often present in the blood long before any signs of joint inflammation, which suggests that the triggering of autoimmunity may occur at sites other than the joints (for example, in the lung)...
December 5, 2016: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/27912794/a-genetic-risk-score-composed-of-rheumatoid-arthritis-risk-alleles-hla-drb1-haplotypes-and-response-to-tnfi-therapy-results-from-a-swedish-cohort-study
#2
Xia Jiang, Johan Askling, Saedis Saevarsdottir, Leonid Padyukov, Lars Alfredsson, Sebastien Viatte, Thomas Frisell
BACKGROUND: To prevent debilitating and irreversible joint damage, rheumatoid arthritis (RA) is often treated with tumor necrosis factor inhibitor (TNFi), but many patients do not respond to this costly therapy. Few predictors for response are known, and it has been proposed that genetic factors which influence the development of RA may also influence disease severity and response to therapy. Several previous studies have attempted to confirm this but results remain inconclusive. We expand on previous studies by including more RA risk alleles, and maximize power by combining them into a genetic risk score...
December 3, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27911913/effect-of-osteoprotegerin-and-dickkopf-related-protein-1-on-radiological-progression-in-tightly-controlled-rheumatoid-arthritis
#3
Carmen Gómez-Vaquero, Irene Martín, Estibaliz Loza, Loreto Carmona, José Ivorra, José Antonio Narváez, Javier Hernández-Gañán, Pedro Alía, Javier Narváez
OBJECTIVE: To analyze the association between circulating osteoprotegerin (OPG) and Dickkopf-related protein 1 (DKK-1) and radiological progression in patients with tightly controlled rheumatoid arthritis (RA). METHODS: Serum levels of OPG and DKK-1 were measured in 97 RA patients who were treated according to a treat-to-target strategy (T2T) aimed at remission (DAS28<2.6). Radiologic joint damage progression was assessed by changes in the total Sharp-van der Heijde score (SHS) on serial radiographs of the hands and feet...
2016: PloS One
https://www.readbyqxmd.com/read/27906052/antibody-responses-to-de-novo-identified-citrullinated-fibrinogen-peptides-in-rheumatoid-arthritis-and-visualization-of-the-corresponding-b-cells
#4
Vijay Joshua, Loes Schobers, Philip J Titcombe, Lena Israelsson, Johan Rönnelid, Monika Hansson, Anca I Catrina, Ger J M Pruijn, Vivianne Malmström
BACKGROUND: Antibodies against citrullinated proteins (ACPA) are common in patients with rheumatoid arthritis (RA). ACPA can appear before disease onset and target many self-antigens. Citrullinated fibrin/fibrinogen represents a classical ACPA target antigen, and mass spectrometry of RA synovial fluid reveals elevated citrullinated (cit) fibrinogen (Fib) peptides compared to non-RA controls. We investigated the extent to which these less-studied peptides represent autoantibody targets and sought to visualize the corresponding cit-Fib-reactive B cells in RA patients...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27906045/smoking-is-associated-with-the-concurrent-presence-of-multiple-autoantibodies-in-rheumatoid-arthritis-rather-than-with-anti-citrullinated-protein-antibodies-per-se-a-multicenter-cohort-study
#5
Tineke J van Wesemael, Sofia Ajeganova, Jennifer Humphreys, Chikashi Terao, Ammar Muhammad, Deborah P M Symmons, Alex J MacGregor, Ingiäld Hafström, Leendert A Trouw, Annette H M van der Helm-van Mil, Tom W J Huizinga, Tsuneyo Mimori, René E M Toes, Fumihiko Matsuda, Björn Svensson, Suzanne M M Verstappen, Diane van der Woude
BACKGROUND: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27900357/datasets-of-yy1-expression-in-rheumatoid-arthritis-patients
#6
Jinpiao Lin, Yujue He, Junmin Chen, Zhiyong Zeng, Bin Yang, Qishui Ou
The data presented in this article are related to the research article entitled "A critical role of transcription factor YY1 in rheumatoid arthritis by regulation of interleukin-6" (J. Lin, Y. He, J. Chen, Z. Zeng, B. Yang, Q. Ou, 2016) [1]. The article describes YY1 overexpression is specific for RA, but not for SLE, SS, DM or MCTD. In early RA, YY1 expression is also increased. In asymptomatic subjects with RF or ACPA positive who have high risk for developing RA, the YY1 expression is not increased obviously...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27895639/netosis-as-source-of-autoantigens-in-rheumatoid-arthritis
#7
REVIEW
Elisa Corsiero, Federico Pratesi, Edoardo Prediletto, Michele Bombardieri, Paola Migliorini
In neutrophils (but also in eosinophils and in mast cells), different inflammatory stimuli induce histone deimination, chromatin decondensation, and NET formation. These web-like structures that trap and kill microbes contain DNA, cationic granule proteins, and antimicrobial peptides, but the most abundant proteins are core histones. Histones contained in NETs have been deiminated, and arginines are converted in citrullines. While deimination is a physiological process amplified in inflammatory conditions, only individuals carrying genetic predisposition to develop rheumatoid arthritis (RA) make antibodies to deiminated proteins...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27887639/prevalence-sensitivity-and-specificity-of-antibodies-against-carbamylated-proteins-in-a-monocentric-cohort-of-patients-with-rheumatoid-arthritis-and-other-autoimmune-rheumatic-diseases
#8
Arbi Pecani, Cristiano Alessandri, Francesca Romana Spinelli, Roberta Priori, Valeria Riccieri, Manuela Di Franco, Fulvia Ceccarelli, Tania Colasanti, Monica Pendolino, Riccardo Mancini, Simona Truglia, Cristiana Barbati, Marta Vomero, Danilo Sabatinelli, Francesca Morello, Guido Valesini, Fabrizio Conti
BACKGROUND: Antibodies against carbamylated proteins (anti-CarP) have been recently identified in the sera of patients with rheumatoid arthritis (RA). The objective of the study was to evaluate the prevalence, sensitivity and specificity of anti-CarP compared to anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF), replicating the existing data in a large cohort of Italian patients with RA and extending the evaluation to other autoimmune rheumatic diseases (AIRDs). METHODS: Serum samples (n = 607) from 309 patients with RA, 200 disease controls and 98 normal healthy subjects (NHS) were evaluated...
November 25, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27876072/high-specificity-bioinformatics-framework-for-epigenomic-profiling-of-discordant-twins-reveals-specific-and-shared-markers-for-acpa-and-acpa-positive-rheumatoid-arthritis
#9
David Gomez-Cabrero, Malin Almgren, Louise K Sjöholm, Aase H Hensvold, Mikael V Ringh, Rakel Tryggvadottir, Juha Kere, Annika Scheynius, Nathalie Acevedo, Lovisa Reinius, Margaret A Taub, Carolina Montano, Martin J Aryee, Jason I Feinberg, Andrew P Feinberg, Jesper Tegnér, Lars Klareskog, Anca I Catrina, Tomas J Ekström
BACKGROUND: Twin studies are powerful models to elucidate epigenetic modifications resulting from gene-environment interactions. Yet, commonly a limited number of clinical twin samples are available, leading to an underpowered situation afflicted with false positives and hampered by low sensitivity. We investigated genome-wide DNA methylation data from two small sets of monozygotic twins representing different phases during the progression of rheumatoid arthritis (RA) to find novel genes for further research...
November 22, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27867000/neuromodulatory-effects-of-the-dorsal-hippocampal-endocannabinoid-system-in-dextromethorphan-morphine-induced-amnesia
#10
Zahra Ghasemzadeh, Ameneh Rezayof
Dextromethorphan which is an active ingredient in many cough medicines has been previously shown to potentiate amnesic effect of morphine in rats. However, the effect of dextromethorphan, that is also a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in combination with morphine on hippocampus-based long term memory has not been well characterized. The aim of the present study was to assess the possible role of endocannabinoid system of the dorsal hippocampus in dextromethorphan /morphine-induced amnesia...
November 17, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27863183/evidence-for-immune-relevance-of-prevotella-copri-a-gut-microbe-in-patients-with-rheumatoid-arthritis
#11
Annalisa Pianta, Sheila Arvikar, Klemen Strle, Elise E Drouin, Qi Wang, Catherine E Costello, Allen C Steere
OBJECTIVE: Prevotella copri, an intestinal microbe, may over-expand in stool samples of patients with new-onset rheumatoid arthritis (NORA), but it is not yet clear whether the organism has immune relevance in RA pathogenesis. METHODS: HLA-DR-presented peptides (T cell epitopes) from P. copri were sought directly from patients' synovial tissue or peripheral blood mononuclear cells (PBMC) using tandem mass spectrometry, followed by testing the antigenicity of peptides or their source proteins using samples from RA patients or comparison groups...
November 18, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27859022/igg1-and-igg4-anti-ccp-associate-with-shared-epitope-whereas-igg2-anti-ccp-associates-with-smoking-in-patients-with-recent-onset-rheumatoid-arthritis-the-swedish-tira-project
#12
Klara Martinsson, Anders Johansson, Alf Kastbom, Thomas Skogh
Given the possible importance of anti-citrullinated peptide/protein antibodies (ACPA) for initiation and progression of rheumatoid arthritis (RA), extended knowledge about the different isotypes and subclasses are important. In the present study we analysed the IgG subclasses regarding reactivity against citrullinated peptides (anti-CCP) among 504 clinically well-characterized patients with recent-onset RA in relation to smoking habits, shared epitope (SE) status, and IgA and pan IgG anti-CCP antibodies. All patients, regardless of pan IgG anti-CCP status, were analysed for IgG1-4 CCP reactivity...
November 17, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27843577/age-affects-joint-space-narrowing-in-patients-with-early-active-rheumatoid-arthritis
#13
X M E Matthijssen, G Akdemir, I M Markusse, T Stijnen, N Riyazi, K H Han, C Bijkerk, P J S M Kerstens, W F Lems, T W J Huizinga, C F Allaart
BACKGROUND: Joint space narrowing (JSN) in rheumatoid arthritis (RA) may be a manifestation of (primary) osteoarthritis becoming more prominent with age. We investigated the severity and predictors of JSN progression among different age groups. METHODS: 10-year follow-up data of the BeSt study, a randomised controlled treat-to-target trial in early RA were used. Annual X-rays of hands and feet were scored using the Sharp/van der Heijde score (SHS). Subgroups were defined by age at baseline: ≥55, ≥40<55 and <40 years...
2016: RMD Open
https://www.readbyqxmd.com/read/27829677/undifferentiated-arthritis-abatacept-for-treating-acpa-negative-ua
#14
Jessica McHugh
No abstract text is available yet for this article.
November 10, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27824549/acpas-are-much-more-than-diagnostic-autoantibodies
#15
REVIEW
Abdulla Watad, Howard Amital
Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation...
October 31, 2016: Rambam Maimonides Medical Journal
https://www.readbyqxmd.com/read/27824546/citrullination-in-rheumatoid-arthritis-a-process-promoted-by-neutrophil-lysis
#16
REVIEW
Tal Gazitt, Christian Lood, Keith B Elkon
Anti-citrullinated protein antibodies (ACPAs) are highly specific serologic markers for rheumatoid arthritis (RA) and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD) enzymes present in polymorphonuclear cells (PMNs). Calcium ions (Ca(2+)) are required for PAD activation, but the intracellular Ca(2+) concentration in normal cells is much lower than the optimal Ca(2+) concentration needed for PAD activation...
October 31, 2016: Rambam Maimonides Medical Journal
https://www.readbyqxmd.com/read/27821150/comparative-effectiveness-of-treatment-with-the-first-tnf-antagonist-in-monotherapy-the-first-tnf-antagonist-plus-one-conventional-synthetic-disease-modifying-antirheumatic-drug-and-the-first-tnf-antagonist-plus-two-or-more-conventional-synthetic-disease-modifying
#17
Blanca Hernández-Cruz, Esther Márquez-Saavedra, Rafael Caliz-Caliz, Federico Navarro-Sarabia
BACKGROUND: Rheumatoid arthritis (RA) patients are treated with a mean of 3-4 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with or without glucocorticoids (GCs), before the first biologic prescription. The main reasons for change are inefficacy in 30-40 % of patients, and toxicity ≈ 10 %. Thus, they are treated with the first TNF antagonists in monotherapy. The aim of this study was to analyse the csDMARD and GC prescription patterns before and during treatment with the first TNF antagonist, and compare their effectiveness in three groups of patients...
November 8, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27796844/the-complex-role-of-the-lung-in-the-pathogenesis-and-clinical-outcomes-of-rheumatoid-arthritis
#18
REVIEW
Lindsay B Kelmenson, M Kristen Demoruelle, Kevin D Deane
While the primary manifestation of rheumatoid arthritis (RA) is articular disease, extra-articular disease may also occur. In particular, pulmonary disease is a frequent extra-articular manifestation of seropositive RA and a leading cause of morbidity and mortality in this population. This review will highlight studies published in the last several years and will, in particular, discuss the relationship of antibodies to citrullinated protein/peptide antigens (ACPA) and lung disease in patients with RA. We will also review the data regarding the potential role of the lung and generation of RA-related autoantibodies in a period of disease development termed "preclinical RA...
November 2016: Current Rheumatology Reports
https://www.readbyqxmd.com/read/27788229/characterization-of-autoantigens-targeted-by-anti-citrullinated-protein-antibodies-in-vivo-prominent-role-for-epitopes-derived-from-histone-4-proteins
#19
Xiaobo Meng, Peyman Ezzati, Irene Smolik, Charles N Bernstein, Carol Ann Hitchon, Hani S El-Gabalawy
Anti-citrullinated protein antibodies (ACPA) have become an integral part of the clinical definition of rheumatoid arthritis, and are hypothesized to be important in the immunopathogenesis of this autoimmune disease. Several citrullinated proteins have been demonstrated to serve as candidate autoantigens for the ACPA, based on in vitro immune reactions between citrullinated peptides/proteins and RA sera. Yet it remains unclear whether the autoantigens identified in vitro are indeed directly and specifically targeted by the ACPA in vivo...
2016: PloS One
https://www.readbyqxmd.com/read/27777982/a-molecular-signature-of-preclinical-rheumatoid-arthritis-triggered-by-dysregulated-ptpn22
#20
Hui-Hsin Chang, Guang-Yaw Liu, Nishant Dwivedi, Bo Sun, Yuko Okamoto, Jennifer D Kinslow, Kevin D Deane, M Kristen Demoruelle, Jill M Norris, Paul R Thompson, Jeffrey A Sparks, Deepak A Rao, Elizabeth W Karlson, Hui-Chih Hung, V Michael Holers, I-Cheng Ho
A unique feature of rheumatoid arthritis (RA) is the presence of anti-citrullinated protein antibodies (ACPA). Several risk factors for RA are known to increase the expression or activity of peptidyl arginine deiminases (PADs), which catalyze citrullination and, when dysregulated, can result in hypercitrullination. However, the consequence of hypercitrullination is unknown and the function of each PAD has yet to be defined. Th cells of RA patients are hypoglycolytic and hyperproliferative due to impaired expression of PFKFB3 and ATM, respectively...
October 20, 2016: JCI Insight
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